US8260402B2ActiveUtilityA1

Noninvasive measurement of carotenoids in biological tissue

Assignee: ERMAKOV IGOR VPriority: Jun 6, 2008Filed: Jun 6, 2008Granted: Sep 4, 2012
Est. expiryJun 6, 2028(~1.9 yrs left)· nominal 20-yr term from priority
A61B 5/443G01N 2021/4742G01N 21/65G01N 2021/656G01N 2021/4709A61B 5/0075G01N 2201/0618A61B 5/0053G01N 2021/4757G01N 2201/0221G01N 21/4785
69
PatentIndex Score
17
Cited by
29
References
16
Claims

Abstract

A method and apparatus are provided for the determination of carotenoid antioxidants and similar chemical compounds in biological tissue such as living skin. The method and apparatus provide a noninvasive, rapid, accurate, and safe determination of carotenoid levels which in turn can provide diagnostic information of the antioxidant status of tissue. Reflection spectroscopy is used to measure the concentrations of carotenoids and similar substances in tissue. White light is directed upon the area of tissue that is of interest. A small fraction of diffusively scattered light is collected and measured. The tissue is pressured to temporarily squeeze blood out of the measured tissue volume while the reflection spectrum is continuously monitored, displayed, and analyzed in near real time. After an optimal time period of typically 15 seconds, the influence of the dominating hemoglobin and oxyhemoglobin tissue absorptions on the reflection spectra are minimized.

Claims

exact text as granted — not AI-modified
1. A noninvasive method of measuring carotenoid levels in biological tissue, comprising the steps of:
 illuminating a localized region of tissue with light that overlaps the absorption bands of carotenoids in the blue wavelength region at or about 480 nm; 
 illuminating the same region with light outside the carotenoid absorption band in the red wavelength region at or about 620 nm; 
 applying pressure to the localized region for a predetermined period of time so as to reduce the level of blood chromophores in the localized region; 
 using reflection spectroscopy to measure absorbances due to all chromophores remaining after pressurization in the blue and red wavelength regions; and 
 determining the level of carotenoids in the localized region as the difference between the absorbances in the blue and red wavelength regions. 
 
     
     
       2. The method of  claim 1 , wherein the pressure is applied to the localized region of tissue for about 1 to 20 seconds. 
     
     
       3. The method of  claim 1 , further including the step of restricting blood flow to the localized region. 
     
     
       4. The method of  claim 1 , further including the step of:
 recording a dark spectrum D(λ) providing a background signal intensity; 
 measuring and storing a reflectivity standard; and 
 wherein the reflectivity spectrum associated with the level of carotenoids in the localized region is calculated according to the expression: 
 
       
         
           
             
               
                 R 
                 ⁡ 
                 
                   ( 
                   λ 
                   ) 
                 
               
               = 
               
                 
                   
                     
                       
                         T 
                         ⁡ 
                         
                           ( 
                           λ 
                           ) 
                         
                       
                       - 
                       
                         D 
                         ⁡ 
                         
                           ( 
                           λ 
                           ) 
                         
                       
                     
                     
                       
                         S 
                         ⁡ 
                         
                           ( 
                           λ 
                           ) 
                         
                       
                       - 
                       
                         D 
                         ⁡ 
                         
                           ( 
                           λ 
                           ) 
                         
                       
                     
                   
                   · 
                   100 
                 
                 ⁢ 
                 % 
               
             
           
         
         where R(λ) is a normalized reflectivity spectrum, and T(λ), S(λ) and D(λ) are the intensity signals measured at wavelength λ from the tissue and reflectivity standard, respectively, and D(λ) is the signal at any wavelength λ due to the dark spectrum intensity. 
       
     
     
       5. The method of  claim 4 , further including the step of converting the normalized reflectivity spectrum R(λ) into an apparent optical density spectrum A(λ) by taking the decimal logarithm for each spectral data point of the reflectivity spectrum, according to the relation: 
       
         
           
             
               
                 A 
                 ⁡ 
                 
                   ( 
                   λ 
                   ) 
                 
               
               = 
               
                 - 
                 
                   
                     lg 
                     ⁡ 
                     
                       ( 
                       
                         
                           R 
                           ⁡ 
                           
                             ( 
                             λ 
                             ) 
                           
                         
                         100 
                       
                       ) 
                     
                   
                   . 
                 
               
             
           
         
       
     
     
       6. The method of  claim 1 , further including the step of comparing the level of carotenoids with normal biological tissue to assess the risk or presence of malignancy or other disease conditions. 
     
     
       7. The method of  claim 1 , wherein the tissue is human skin. 
     
     
       8. The method of  claim 7 , wherein the skin is on a fingertip or other portion of a hand. 
     
     
       9. A system for measuring carotenoid levels in biological tissue noninvasively, comprising:
 a source of light configured to illuminate a localized region of tissue with light that overlaps the absorption bands of carotenoids in the blue wavelength region at or about 480 nm; 
 a source of light configured to illuminate the same localized region of tissue with light outside the carotenoid absorption band in the red wavelength region at or about 620 nm; 
 a pressurization device configured to apply pressure to the localized region for a predetermined period of time so as to reduce the level of blood chromophores in the localized region; 
 a spectrograph configured to measure absorbances due to all chromophores remaining after pressurization in the blue and red wavelength regions; and 
 a processor configured to determine the level of carotenoids in the localized region as the difference between the absorbances in the blue and red wavelength regions. 
 
     
     
       10. The system of  claim 9 , wherein the pressure is applied to the tissue for about 1 to 20 seconds. 
     
     
       11. The system of  claim 9 , wherein the device for applying pressure is an optically transparent element through which the light and reflection spectra pass. 
     
     
       12. The system of  claim 9 , wherein the device for applying pressure is a lens through which the light and reflection spectra pass. 
     
     
       13. The system of  claim 9 , further including a cuff or other device for restricting blood flow to the localized region. 
     
     
       14. The system of  claim 9 , wherein the light sources are derived from a single white light source substantially spanning the spectral range from about 350 to 900 nm. 
     
     
       15. The system of  claim 9 , wherein the light sources are separate sources, one at or about 480 nm and the other at or about 620 nm. 
     
     
       16. The system of  claim 9 , wherein:
 the device for applying pressure to the localized region for a predetermined period of time is contained in a probe body; 
 light from the source is delivered to the probe through a first optical fiber; and 
 reflectance spectra is carried from the probe body to the spectrograph through a second optical fiber.

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